Congenital and early onset binocular imbalance, including esotropia (ET) and cataracts affect 2-4% of infants in the U.S. Binocular imbalance during visual development has the potential to cause amblyopia and abnormalities in binocular vision. Over 90% of patients with congenital and early onset binocular imbalance require occlusion therapy, spectacle correction, and/or surgery, and many require repeated interventions. Abnormal binocular sensory function is associated with higher risk for multiple eye muscle surgeries, dissociated vertical deviation, latent nystagmus, and amblyopia. Thus, the cost of early onset binocular imbalance is significant. During the current grant period, we found that binocular vision initially develops normally in infantile ET but is disrupted by abnormal binocular experience. This result suggested that very early surgery might prevent the deficit but, although we found a higher prevalence of stereopsis after very early surgery, normal stereoacuity was rare. We propose to pursue this surprising result by investigating the hypothesis that infantile ET is associated with initially normal development of the coarse, peripheral disparity sensitivity but a congenital absence or irreversible abnormality of the disparity sensitivity in the central visual field. Furthermore, we will investigate whether a congenital deficit in central disparity sensitivity is associated with vergence abnormalities in infantile ET. Several of our studies during the current grant support a link between binocular dysfunction and amblyopia. We will test the hypotheses that asymmetric binocular interactions predispose some esotropic infants and children to develop amblyopia, that weaning from occlusion therapy acts to diminish asymmetry, and that persistent residual amblyopia results from asymmetry that resists treatment. Relatively little is known about amblyopia in children <3 years of age. In the upcoming grant period, we will characterize the natural history of amblyopia during the first 3 years of life, determine whether different patterns of response to treatments and different risks associated with treatments are present in this age range, and evaluate new approaches to the detection and monitoring of amblyopia in infants and young children. While we have a good grasp on the effects of unilateral deprivation amblyopia and treatment protocols for dense congenital unilateral cataracts, a number of important questions remain about the effects of other types of cataracts on the developing visual system. We propose to define the critical period for visual acuity outcome in dense congenital bilateral cataracts, examine the effects of partial cataracts on visual maturation, and evaluate the critical period(s) for ocular motor development in children with dense congenital cataracts. Taken together, these five Aims directly address a stated goal of the NEI National Plan, namely "to investigate the development of visual function in children at high risk for amblyopia and strabismus, determine underlying mechanisms, and develop and disseminate information about detection methods and therapeutic interventions for restoring normal vision." PUBLIC HEALTH RELEVANCE: Congenital and early onset binocular imbalance due, for example, to esotropia and cataracts affect 2-4% of infants in the U.S. Over 90% of patients with congenital and early onset binocular imbalance require occlusion therapy, spectacle correction, and/or surgery, and many require repeated interventions. The aim of the proposed studies is to define the necessary and sufficient conditions for the development of normal binocular vision and to enhance treatment outcomes of patients with conditions that are associated with congenital and early onset binocular imbalance.